Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000697638 | SCV000826261 | pathogenic | Peroxisome biogenesis disorder | 2023-08-10 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This sequence change affects an acceptor splice site in intron 15 of the PEX6 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in PEX6 are known to be pathogenic (PMID: 10408779, 21031596, 31831025). This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individuals with clinical features of Zellweger syndrome (Invitae). ClinVar contains an entry for this variant (Variation ID: 575426). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. This variant disrupts the c.2667-2A nucleotide in the PEX6 gene. Other variant(s) that disrupt this nucleotide have been determined to be pathogenic (PMID: 19877282). This suggests that this nucleotide is clinically significant, and that variants that disrupt this position are likely to be disease-causing. |